Epilepsy More than Doubles Mortality Risk for Veterans of Recent Wars

by U.S. Medicine

February 14, 2017

Study Emphasizes Comorbid Disease Management in Epilepsy Patients

By Brenda L. Mooney

SAN ANTONIO—Meeting criteria for an epilepsy diagnosis significantly raises the risk of death among veterans who served in Iraq and Afghanistan, a new study has revealed.

Unadjusted cumulative mortality estimates of Iraq and Afghanistan war veterans during the 60-month follow-up period after initial provider visit, by epilepsy status — Veterans Health Administration, United States, 2011–2015

In fact, Iraq and Afghanistan veterans (IAVs) with epilepsy were found to be 2.6 times more likely to die between 2011 and 2015 than similar veterans without epilepsy, according to a report published in the Morbidity and Mortality Weekly Report and presented last month at the American Epilepsy Society meeting in Houston.1

The study, conducted by the South Texas Veterans Health Care System, the University of Texas Health Science Center at San Antonio, the national Centers for Disease Control and Prevention and a number of other VAMCs, used records of more than 320,000 IAVs receiving VA care in 2010 and 2011 to reach the conclusions.

“Veterans with epilepsy who were deployed in the Iraq and Afghanistan conflicts could benefit from evidence-based chronic disease self-management programs to reduce physical and psychiatric comorbidity, and linkages to U.S. Department of Veteran Affairs clinical health care providers and other community health and social service providers,” the researchers recommend.

Focusing on 2,187 veterans who met the criteria for epilepsy, examination of mortality over the next five years revealed that approximately five times more IAVs with epilepsy died by the end of 2015 than similar IAVs without epilepsy. A second analysis controlling for co-occurring conditions—such as cardiac disease, stroke, cancer and mental health conditions—also was conducted to determine if epilepsy uniquely contributed to mortality.

“Similar to studies of civilian samples, we found that cancer, stroke and cardiac disease were strong predictors of five-year mortality. But, even after controlling for the impact of these comorbid conditions, we still found a substantial effect for epilepsy,” explained lead author Mary Jo Pugh, PhD, RN, a research health scientist for the Veterans Evidence-based Research, Dissemination, and Implementation Center at the South Texas Veterans Health Care System and professor of epidemiology, biostatistics and medicine at the UT Health Science Center. “After controlling for comorbidities, IAVs with epilepsy were about 2.6 times more likely to die during the follow-up period than similar veterans without epilepsy.””Because federal databases at the time the study was conducted did not include causes of death, the report does not speculate on whether mortality was linked to suicidality, car accidents, heart attack, cancer or sudden unexplained death in epilepsy, Pugh added.

Part of the problem is that a range of comorbidities on top of seizures can present healthcare providers with competing demands, she pointed out, noting, “If you have a patient who comes in and is having seizures, that is often the focus of care, because persistent seizures can be life-threatening and have a substantial effect on quality of life. But chronic disease management for other conditions is also needed. We need to take a holistic approach in epilepsy care. We need to take care of epilepsy and other conditions that affect patients’ health, quality of life and, ultimately, mortality.””The age-adjusted prevalence of seizure disorder in U.S. deployed in Iraq and Afghanistan conflicts is 6.1 per 1,000 persons, compared with 7.1 to 10 per 1,000 persons in the general population, according to the MMWR report.

For this study, veterans whose only seizure medication was either gabapentin or pregabalin were included in the epilepsy group only if they also had an ICD-9-CM 345 diagnosis to minimize false-positive cases because gabapentin and pregabalin are sometimes used for pain management or for other indications.


Epilepsy Related to TBI

Of the more than 87,000 veterans with seizures on anti-epileptic drugs managed by the VHA, 15.8% of them had comorbid traumatic brain injury (TBI) and 24.1% had comorbid post-traumatic stress disorder (PTSD), according to a recent study. Yet, those percentages increased to 52% for TBI and 70.4% for PTSD in veterans who served in Iraq and Afghanistan.

The article, published in the Journal of Rehabilitation Research and Development, noted that PTSD and TBI are risk factors for both epilepsy and psychogenic nonepileptic seizures (PNES).2

Because epilepsy typically results in persons being excluded from military service, according to the article, the condition usually develops in veterans during or after military service, accounting for the lower age-adjusted prevalence of epilepsy in IAV.

DoD physical standards preclude enlistment of those under treatment for seizure disorders and require a five-year period without any seizures or treatment for seizures prior to enlistment.

In the general population, the study notes, mortality in those with epilepsy is higher among persons with psychiatric and physical comorbidity, with the most-common causes of death including cancer, cardiovascular disease, cerebrovascular disease and pneumonia.

Furthermore, “patients with persistent seizures and diagnoses of symptomatic or cryptogenic epilepsies have the largest excess mortality,” according to the researchers, who added, “Consistent with other studies, excess mortality in veterans with epilepsy might be associated with both epilepsy (e.g., poorly-controlled seizures, sudden unexpected death in epilepsy) and other individual or environmental factors (e.g., depression, high-risk behaviors and social isolation).”

Limitations of the study, the authors state, are that only 61% of IAV are being treated at the VA and, therefore, were included in the research; that epilepsy care received outside the VA was not documented; because veterans differ demographically from the general population; and that some IAV with psychogenic nonepileptic seizures (PNES) and diagnosed with epilepsy or misclassified as having epilepsy could have been inadvertently included in the analysis.

“Healthcare providers should strive to ensure that veterans with epilepsy receive appropriate treatment to maximize seizure control,” suggests the MMWR article. “The VA implemented the Epilepsy Centers of Excellence, a hub-and-spoke model of care, to increase access to comprehensive, multidisciplinary epilepsy specialty care in response to the risk for epilepsy in the IAV population with traumatic brain injury. However, a significantly higher prevalence of comorbidities in this population suggests that closer integration of primary care, epilepsy specialty care and mental health care might be needed to reduce excess mortality. For veterans with epilepsy, public health agencies, including the VA, can implement evidence-based chronic disease self-management programs and supports that target physical and psychiatric comorbidity, study long-term outcomes, including cause of death, and ensure linkages to appropriate VA clinical and community health care and social service providers.”

The study is touted as the first to examine mortality in veterans with epilepsy, according to the authors, and even is unique compared to studies of epilepsy-related mortality in the United States.

While civilian studies in the United States have consisted of small samples in localized areas, this study looks at a much-larger population of IAVs. That is possible, according to Pugh, because of the growing availability of electronic health records.


  1. Pugh MJ, Van Cott AC, Amuan M, et al. Epilepsy Among Iraq and Afghanistan War VeteransUnited States, 2002-2015. MMWR Morb Mortal Wkly Rep 2016;65:1224–1227. DOI: http://dx.doi.org/10.15585/mmwr.mm6544a5.
  2. Rehman R, Kelly PR, Husain AM, Tran TT. Characteristics of Veterans diagnosed with seizures within Veterans Health Administration. J Rehabil Res Dev. 2015;52(7):751-62. doi: 10.1682/JRRD.2014.10.0241. PubMed PMID: 26745205.

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